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1.
An. pediatr. (2003. Ed. impr.) ; 90(3): 180-186, mar. 2019. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-178371

RESUMO

Introducción: La dieta baja en FODMAP (acrónimo en inglés de polioles, monosacáridos, disacáridos y oligosacáridos fermentables) ha demostrado eficacia como tratamiento del síndrome de intestino irritable en adultos, siendo escasos los estudios en niños. Nuestro objetivo es analizar la implantación de esta dieta como tratamiento del dolor abdominal crónico funcional en población pediátrica de un área mediterránea, y su respuesta a esta. Material y métodos: Se elaboró una tabla clasificando los alimentos según su contenido en FODMAP, y se diseñó un "Diario de síntomas y deposiciones" para recoger los datos. Posteriormente se realizó un estudio prospectivo con niños con dolor abdominal crónico funcional de nuestra Unidad de Gastroenterología Pediátrica. Resultados: Se reclutaron 22 pacientes, 20 de los cuales completaron el estudio. Se recogieron durante 3 días datos sobre el dolor abdominal; posteriormente recibieron dieta baja en FODMAP 2 semanas, y al finalizarla recogieron de nuevo dichos datos. Tras la dieta se objetivó disminución en frecuencia diaria de episodios de dolor abdominal (1,16 [RIQ: 0,41-3,33] frente a 2 [RIQ: 1,33-6,33] inicialmente, p = 0,024), menor intensidad del dolor (1,41 cm [RIQ: 0,32-5,23] frente a 4,63 cm [RIQ: 2,51-6,39] inicial, p = 0,035, medido mediante Escala Visual Analógica de 10 cm), menor interferencia con la actividad diaria y menos síntomas acompañantes. Solo un 15% de los pacientes consideraron la dieta difícil. Conclusiones: La implantación de una dieta baja en FODMAP durante 2 semanas en una población pediátrica mediterránea con dolor abdominal crónico funcional es posible utilizando dietas adaptadas, es bien valorada por los pacientes, y su evaluación mediante herramientas objetivas muestra mejoría en los síntomas de dolor abdominal


Introduction: The low FODMAP diet (fermentable oligosaccharides, monosaccharides, disaccharides, and polyols) has shown to be effective in adult patients with irritable bowel syndrome, but there are few studies on paediatric patients. The aim of this study is to assess the implementation and the outcomes of a low FODMAP diet in the treatment of functional abdominal pain in children from a Mediterranean area. Material and methods: A table was designed in which foods were classified according to their FODMAP content, as well as a 'Symptoms and Stools Diary'. A prospective study was conducted on children with functional abdominal pain in our Paediatric Gastroenterology Unit. Results: A total of 22 patients were enrolled in the trial, and 20 completed it. Data were collected of the abdominal pain features over a period of 3 days, and then patients followed a two-week low FODMAP diet. Afterwards, information about abdominal pain features was collected again. After the diet, they showed fewer daily abdominal pain episodes compared to baseline (1.16 [IQR: 0.41-3.33] versus 2 [IQR: 1.33-6.33] daily episodes, P = .024), less pain severity compared to baseline (1.41 cm [IQR: 0.32-5.23] versus 4.63 cm [IQR: 2.51-6.39] measured by 10-cm Visual Analogue Scale, P = .035), less interference with daily activities, and less gastrointestinal symptoms. Only 15% of patients found it difficult to follow the diet. Conclusions: The implementation of a low FODMAP diet for 2 weeks in a Mediterranean paediatric population diagnosed with functional abdominal pain is possible with adapted diets. It was highly valued by patients, and they showed an improvement in abdominal pain symptoms assessed by objective methods


Assuntos
Humanos , Masculino , Feminino , Criança , Dor Abdominal/dietoterapia , Implementação de Plano de Saúde/normas , Desidrogenase do Álcool de Açúcar/uso terapêutico , Monossacarídeos/uso terapêutico , Dissacarídeos/uso terapêutico , Oligossacarídeos/uso terapêutico , Alimentos/classificação , Estudos Prospectivos , Microbioma Gastrointestinal
2.
Biomed Pharmacother ; 112: 108624, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30784921

RESUMO

Rheumatoid arthritis (RA) is a chronic autoimmune disease of synovial inflammation and joint destruction. This study reports anti-arthritic potential of opuntioside-I opuntiol, and its gold and silver nanoparticles (NPs) against Complete Freund's Adjuvant (CFA)-induced arthritic rats. The mechanistic studies were performed targeting TLRs (TLR-2 and TLR-4) and cytokines (IL-1ß and TNF-α) expressions to validate their anti-inflammatory and immuno-modulatory response. The nano-formulations were successfully characterized employing Atomic Force Microscopy (AFM) and Dynamic Light Scattering (DLS) analysis. Opuntiol and opuntioside (OP and OPG: 10, 50 and 100 mg/kg) and opuntiol-coated silver and gold NPs (OP-AgNPs and OP-AuNPs: 0.5, 1 and 3 mg/kg) treatments in arthritic rat have shown minimal arthritic score exhibiting mild to moderate articular changes and tissue swelling in ankle joints. Radiographic examination reveals significant reduction in synovitis with improvement in joints degenarative changes in the presence of aforementioned treatments. Likewise, histology of rat ankle joints depicted comparatively lesser influx of inflammatory cells and diminished granulamatous inflammation. Moreover, treatment groups suppressed protein and mRNA expressions of TLRs (TLR-2 and TLR-4) and cytokines (IL-1ß and TNF-α) levels were also significantly declined in the presence of OPG, OP and its NPs comparing to arthritic control. This investigation concludes, the tested compounds and nano-formulations successfully restored the disease progression in CFA-induced arthritic rat owing to their immunomodulatory and anti-inflammatory potentials and can be considered for RA targeted therapy to address the utmost challenges of the disease.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Experimental/tratamento farmacológico , Ácidos Cumáricos/uso terapêutico , Nanopartículas Metálicas/uso terapêutico , Monossacarídeos/uso terapêutico , Receptor 2 Toll-Like/antagonistas & inibidores , Receptor 4 Toll-Like/antagonistas & inibidores , Animais , Antirreumáticos/administração & dosagem , Antirreumáticos/química , Artrite Experimental/imunologia , Artrite Experimental/metabolismo , Ácidos Cumáricos/administração & dosagem , Ácidos Cumáricos/química , Feminino , Adjuvante de Freund , Ouro/química , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Monossacarídeos/administração & dosagem , Monossacarídeos/química , Ratos Wistar , Prata/química
3.
Molecules ; 23(8)2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30071672

RESUMO

Background: Allergic disease is a common clinical disease. Natural products provide an important source for a wide range of potential anti-allergic agents. This study was designed to evaluate the anti-allergic activities of the water-soluble polysaccharides extracted and purified from Saposhnikoviae Radix (SRPS). The composition and content of monosaccharides were determined to provide a material basis. Methods: An ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established to determine the composition and content of SRPS. 2,4-dinitrofluorobenzene (DNFB) induced a delayed-type hypersensitivity (DTH) mouse model orally administrated SRPS for seven consecutive days. Ear swelling, organ index, and serum IgE levels were observed to evaluate the anti-allergic activities. Results: The UPLC-MS/MS analysis showed that SRPS was consisted of eight monosaccharides including galacturonic acid, mannose, glucose, galactose, rhamnose, fucose, ribose, and arabinose with a relative molar ratio of 4.42%, 7.86%, 23.69%, 12.06%, 3.10%, 0.45%, 0.71%, and 47.70%, respectively. SRPS could effectively reduce ear swelling, a thymus index, and a serum IgE levels. Conclusions: The method was simple, rapid, sensitive, and reproducible, which could be used to analyze and determine the monosaccharide composition of SRPS. The vivo experiments demonstrated that SRPS may effectively inhibit development of DNFB-induced DTH. SRPS is a novel potential resource for natural anti-allergic drugs.


Assuntos
Apiaceae/química , Cromatografia Líquida de Alta Pressão/métodos , Monossacarídeos/análise , Espectrometria de Massas em Tandem/métodos , Animais , Antialérgicos/análise , Antialérgicos/uso terapêutico , Anti-Inflamatórios/análise , Anti-Inflamatórios/uso terapêutico , Dinitrofluorbenzeno/toxicidade , Modelos Animais de Doenças , Feminino , Hipersensibilidade Tardia/induzido quimicamente , Hipersensibilidade Tardia/tratamento farmacológico , Camundongos , Monossacarídeos/uso terapêutico , Polissacarídeos/análise , Polissacarídeos/uso terapêutico
4.
Dig Dis ; 36(4): 271-280, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29763907

RESUMO

BACKGROUND AND AIM: To evaluate the usefulness of a low FODMAP (Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols) diet on patients with irritable bowel syndrome (IBS), non-active inflammatory bowel diseases (IBD), and celiac disease (CD) on a gluten-free diet (GFD). METHODS: Dietetic interventional prospective study. IBS, IBD, and CD subjects were evaluated to check if they fulfilled the Rome III criteria. Each subject was educated to follow a low FODMAP diet after being evaluated by filling out questionnaires that assessed the quality of life (QoL) and symptoms experienced (IBS-SSS and SF-36), and was reevaluated after 1 and 3 months. RESULTS: One hundred twenty-seven subjects were enrolled: 56 with IBS, 30 with IBD, and 41 with CD. IBS-SSS showed that abdominal symptoms improved after 1 and 3 months of diet in all subjects, with significant difference among the 3 groups at T0 (average scores IBS: 293 ± 137, IBD: 206 ± 86, CD: 222 ± 65, p < 0.001), but no difference at T3 (IBS: 88 ± 54, IBD: 73 ± 45, CD: 77 ± 49, p = ns). By analyzing the SF-36 questionnaire, we did not observe any difference between the 3 groups, in terms of response to diet (p = ns), we observed a clinical improvement from T0 to T3 for most of the questionnaire's domains. CONCLUSIONS: A low FODMAP diet could be a valid option to counter -abdominal symptoms in patients with IBS, non-active IBD, or CD on a GFD, and thus, improve their QoL and social -relations.


Assuntos
Doença Celíaca/dietoterapia , Dissacarídeos/uso terapêutico , Doenças Inflamatórias Intestinais/dietoterapia , Síndrome do Intestino Irritável/dietoterapia , Monossacarídeos/uso terapêutico , Oligossacarídeos/uso terapêutico , Polímeros/uso terapêutico , Adulto , Idoso , Dieta Livre de Glúten , Feminino , Fermentação , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
5.
Oxid Med Cell Longev ; 2018: 4757893, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29507651

RESUMO

Diabetes is a metabolic disorder with multifactorial and heterogeneous etiologies. Two types of diabetes are common among humans: type 1 diabetes that occurs when the immune system attacks and destroys insulin and type 2 diabetes, the most common form, that may be caused by several factors, the most important being lifestyle, but also may be determined by different genes. Honey was used in folk medicine for a long time, but the health benefits were explained in the last decades, when the scientific world was concerned in testing and thus explaining the benefits of honey. Different studies demonstrate the hypoglycemic effect of honey, but the mechanism of this effect remains unclear. This review presents the experimental studies completed in the recent years, which support honey as a novel antidiabetic agent that might be of potential significance for the management of diabetes and its complications and also highlights the potential impacts and future perspectives on the use of honey as an antidiabetic agent.


Assuntos
Diabetes Mellitus/dietoterapia , Mel , Hipoglicemiantes/uso terapêutico , Animais , Humanos , Monossacarídeos/uso terapêutico
6.
PLoS One ; 12(8): e0182942, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28806407

RESUMO

BACKGROUND: Irritable bowel syndrome (IBS) and functional digestive tract disorders, e.g. functional bloating, carbohydrate maldigestion and intolerances, are very common disorders frequently causing significant symptoms that challenge health care systems. A low Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols (FODMAP) diet is one of the possible therapeutic approaches for decreasing abdominal symptoms and improving quality of life. OBJECTIVES: We aimed to meta-analyze data on the therapeutic effect of a low-FODMAP diet on symptoms of IBS and quality of life and compare its effectiveness to a regular, standard IBS diet with high FODMAP content, using a common scoring system, the IBS Symptom Severity Score (IBS-SSS). METHODS: A systematic literature search was conducted in PubMed, EMBASE and the Cochrane Library as well as in the references in a recent meta-analysis. Adult patients diagnosed with IBS according to the Rome II, Rome III, Rome IV or NICE criteria were included in the analysis. STATISTICAL METHODS: Mean differences with 95% confidence intervals were calculated from studies that contained means, standard deviation (SD) or mean differences and SD of differences and p-values. A random effect model was used because of the heterogeneity (Q test (χ2) and I2 indicator). A p-value of less than 0.05 was chosen to indicate a significant difference. RESULTS: The literature search yielded 902 publications, but only 10 were eligible for our meta-analysis. Both regular and low-FODMAP diets proved to be effective in IBS, but post-diet IBS-SSS values were significantly lower (p = 0.002) in the low-FODMAP group. The low-FODMAP diet showed a correlation with the improvement of general symptoms (by IBS-SSS) in patients with IBS. CONCLUSIONS: This meta-analysis provides high-grade evidence of an improved general symptom score among patients with irritable bowel syndrome who have maintained a low-FODMAP diet compared to those on a traditional IBS diet, therefore showing its superiority to regular IBS dietary therapy. These data suggest that a low-FODMAP diet with dietitian control can be a candidate for first-line therapeutic modality in IBS. Because of a lack of data, well-planned randomized controlled studies are needed to ascertain the correlation between improvement of separate key IBS symptoms and the effect of a low-FODMAP diet.


Assuntos
Dieta , Dissacarídeos/uso terapêutico , Fermentação , Síndrome do Intestino Irritável/dietoterapia , Monossacarídeos/uso terapêutico , Polímeros/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ensaios Clínicos como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Adulto Jovem
7.
Nutr. hosp ; 34(3): 667-674, mayo-jun. 2017. tab
Artigo em Inglês | IBECS | ID: ibc-164125

RESUMO

Introduction: Fibromyalgia is a chronic rheumatic disease producing widespread pain, associated to a major comorbidity -irritable bowel syndrome. Low FODMAPS diet (low fermentable oligo-di-mono-saccharides and polyols diet) has been effective in controlling irritable bowel syndrome symptoms. Overweight is an aggravating factor for fibromyalgia. We studied effects of low fermentable oligo-di-mono-saccharides and polyols diets on fibromyalgia symptoms and weight status. Methods: A longitudinal study was performed on 38 fibromyalgia patients using a four-week, repeated assessment as follow: M1 = first assessments/presentation of individual low fermentable oligo-di-mono-saccharides and polyols diet; M2 = second assessments/reintroduction of FODMAPs; M3 = final assessments/nutritional counselling. The assessment instruments applied were: Fibromyalgia Survey Questionnaire (FSQ); Severity Score System (IBS-SSS); visual analogic scale (VAS). Body mass-index/composition and waist circumference (WC) were also measured. Daily macro-micronutrients and FODMAP intake were quantified at each moment of the study. Results: The studied cohort was 37% overweight, 34% obese (average body mass-index 27.4 ± 4.6; excess fat mass 39.4 ± 7%). Weight, body mass-index and waist circumference decreased significantly (p < 0.01) with low fermentable oligo-di-mono-saccharides and polyols diet, but no significant effect on body composition was observed. All fibromyalgia symptoms, including somatic pain, declined significantly post-LFD (p < 0.01); as well for severity of fibromyalgia [Fibromyalgia survey questionnaire: M1 = 21.8; M2 = 16.9; M3 = 17.0 (p < 0.01)]. The intake of essential nutrients (fiber, calcium, magnesium and vitamin D) showed no significant difference. The significant reduction in FODMAP intake (M1 = 24.4 g; M2 = 2.6g; p < 0.01) reflected the «Diet adherence» (85%). «Satisfaction with improvement of symptoms» (76%), showed correlating with «diet adherence» (r = 0.65; p < 0.01). Conclusions: Results are highly encouraging, showing low fermentable oligo-di-mono-saccharides and polyols diets as a nutritionally balanced approach, contributing to weight loss and reducing the severity of FM fibromyalgia symptoms (AU)


Introducción: la fibromialgia es una enfermedad reumática crónica, que tiene unas importantes comorbilidades-síndrome del intestino irritable (SII). La dieta baja en FODMAPs (low fermentable oligo-di-mono-saccharides and polyols diet) ha sido eficaz en el tratamiento del síndrome del intestino irritable. El sobrepeso es un factor agravante. Se estudiaron los efectos nutricionales del FODMAPs en la fibromialgia. Métodos: estudio longitudinal en 38 pacientes con fibromialgia en el que se utilizó una evaluación repetida, durante cuatro semanas, de lo siguiente: Moment 1 (M1) = primeras evaluaciones/presentación de FODMAPs; M2 = segundas evaluaciones/reintroducción de FODMAPs; M3 = evaluaciones finales/asesoramiento nutricional. Instrumentos de evaluación: Fibromialgia Survey Questionnaire; síndrome del intestino irritable (IBS-SSS), escala visual analógica (EVA) y parámetros antropométricos. Cuantificación en todo momento de las ingestas diarias de macro/micro nutrientes y FODMAPs. Resultados: el estudio de cohorte mostró 37% de sobrepeso y 34% obesidad; índice de masa corporal = 27,4 ± 4,6; masa grasa = 39,4 ± 7%. El peso y la circunferencia de la cintura disminuyeron significativamente con FODMAPs, pero no cambió la composición corporal. Los síntomas y la severidad de la fibromialgia (FSQ: M1 = 21,8; M2 = 16,9; M3 = 17,0) se redujeron significativamente después de FODMPAs (p < 0,01). No fueron observadas diferencias significativas en el consumo de nutrientes esenciales, especialmente la fi bra, calcio, magnesio y vitamina D. El «seguimiento de la dieta» fue del 85% con reducción significativa de la ingesta de FODMAPs (p < 0,01: M1 = 24,4 g; M2 = 2,6 g). «La satisfacción con la mejora de los síntomas» (76%) se correlacionó con el «seguimiento de la dieta» (r = 0,65; p < 0,01). Conclusiones: los resultados son muy alentadores, mostrando FODMAPs como un enfoque equilibrado nutricionalmente, que contribuyó a la pérdida de peso y redujo significativamente la severidad de la FM (AU)


Assuntos
Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Fibromialgia/dietoterapia , Monossacarídeos/uso terapêutico , Síndrome do Intestino Irritável/dietoterapia , Carboidratos/uso terapêutico , Avaliação Nutricional , Estado Nutricional/fisiologia , Carboidratos da Dieta/uso terapêutico , Estudos Longitudinais , Antropometria/métodos , Micronutrientes/uso terapêutico , Estudos de Coortes , Perda de Peso , Inquéritos e Questionários , Composição Corporal/fisiologia
8.
Biomed Pharmacother ; 84: 166-176, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27657824

RESUMO

Melanoma is the most malignant type of skin cancer. In recent years, mounting studies have evidenced the involvement of miRNAs in melanoma. One of these miRNAs, miR-124 has been found aberrantly downregulated in a variety of human malignancies. In this study, our results showed that the expression of miR-124 was significantly lower in malignant melanoma tissues and cell lines and miR-124 functioned as a tumor suppressor in melanoma. Moreover, our findings showed that miR-124 exerted anti-tumor effect by directly targeting RLIP76, a stress-inducible non-ABC transporter that plays a crucial role in the development of melanoma. Furthermore, our study also showed that physcion 8-O-ß-glucopyranoside, a natural compound from medicinal plant, could inhibit the proliferation and invasion of melanoma cells by targeting miR-124/RLIP76 signaling.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Proliferação de Células/fisiologia , Emodina/análogos & derivados , Proteínas Ativadoras de GTPase/metabolismo , Melanoma/metabolismo , MicroRNAs/biossíntese , Monossacarídeos/farmacologia , Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Células Cultivadas , Relação Dose-Resposta a Droga , Emodina/farmacologia , Emodina/uso terapêutico , Feminino , Proteínas Ativadoras de GTPase/antagonistas & inibidores , Humanos , Masculino , Melanócitos/efeitos dos fármacos , Melanócitos/metabolismo , Melanoma/tratamento farmacológico , Monossacarídeos/uso terapêutico , Invasividade Neoplásica , Neoplasias Cutâneas , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologia
9.
Cell Death Dis ; 7(9): e2350, 2016 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-27584788

RESUMO

Gouty arthritis is a rheumatic disease that is characterized by the deposition of monosodium urate (MSU) in synovial joints cause by the increased serum hyperuricemia. This study used a three-dimensional (3D) flowing microfluidic chip to screen the effective candidate against MSU-stimulated human umbilical vein endothelial cell (HUVEC) damage, and found kinsenoside (Kin) to be the leading active component of Anoectochilus roxburghi, one of the Chinese medicinal plant widely used in the treatment of gouty arthritis clinically. Cell viability and apoptosis of HUVECs were evaluated, indicating that direct Kin stimulation and conditioned medium (CM) from Kin-treated macrophages both negatively modulated with MSU crystals. Additionally, Kin was capable of attenuating MSU-induced activation of nuclear factor-κB/mitogen-activated protein kinase (NF-κB/MAPK) signaling, targeting IκB kinase-α (IKKα) and IKKß kinases of macrophages and influencing the expressions of NF-κB downstream cytokines and subsequent HUVEC bioactivity. Inflammasome NLR pyrin domain-containing 3 (NALP3) and toll-like receptor 2 (TLR2) were also inhibited after Kin treatment. Also, Kin downregulated CD14-mediated MSU crystals uptake in macrophages. In vivo study with MSU-injected ankle joints further revealed the significant suppression of inflammatory infiltration and endothelia impairment coupled with alleviation of ankle swelling and nociceptive response via Kin treatments. Taken together, these data implicated that Kin was the most effective candidate from Anoectochilus roxburghi to treat gouty arthritis clinically.


Assuntos
4-Butirolactona/análogos & derivados , Artrite Gotosa/tratamento farmacológico , Artrite Gotosa/metabolismo , Avaliação Pré-Clínica de Medicamentos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Macrófagos/metabolismo , Microfluídica/métodos , Monossacarídeos/uso terapêutico , NF-kappa B/metabolismo , 4-Butirolactona/análise , 4-Butirolactona/farmacologia , 4-Butirolactona/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Artrite Gotosa/patologia , Cristalização , Meios de Cultivo Condicionados/farmacologia , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Citoproteção/efeitos dos fármacos , Extremidades/patologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Inflamassomos/metabolismo , Mediadores da Inflamação/metabolismo , Receptores de Lipopolissacarídeos/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/enzimologia , Masculino , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Monossacarídeos/análise , Monossacarídeos/farmacologia , Células RAW 264.7 , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Ácido Úrico
10.
Hepatology ; 64(6): 2135-2150, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27639182

RESUMO

The central purpose of this study was to investigate therapeutic effects of the botanical derivative, kinsenoside (KD), in experimental autoimmune hepatitis (AIH). Treatment with KD substantially reduced hepatic histopathological damage, induced by lymphocyte infiltration and proinflammatory cytokines, in concanavalin A-induced T-cell-mediated hepatitis, and in dendritic cells (DCs) loaded with hepatocellular carcinoma cells (DC/Hepa1-6) induced murine AIH. Interactions between immune cells after KD treatment in AIH were detected by anti-CD8 antibody blocking, CD8+ T cell sorting, and vaccinated mice with KD-pretreated DCs in a DC/Hepa1-6 model. These results showed that KD inhibited the elevated expressions of CD86 and major histocompatibility complex II, densities of chemokine receptor C-C chemokine receptor type 7, and extensive migration to lymph nodes, and increased the programmed death ligand 1 level of DCs, followed by suppressing CD8+ T cells, characterized as low differentiation and cytotoxicity, and eliciting cytokines balance. Furthermore, biochemical analysis, two-dimensional fingerprint screen and three-dimensional molecular docking results showed that KD bound to the vascular endothelial growth factor receptor 2 (VEGFR2) kinase domain, which inhibited the metabolism-related phosphatidylinositol 3 kinase/protein kinase B (PI3K-AKT) pathway in DCs and DC-modulated CD8+ T cells to lower the mitochondrial membrane potential and glucose/lipid utilization ratio in both cells. KD reversed activation of the PI3K-AKT pathway by 740 Y-P (PI3K agonist), thereby impeding the translocation and dimerization of signal transducer and activators of transcription (STAT) 3 and synergistically blocking the inflammation-related Janus kinase (JAK) 2/STAT3 pathway in DCs and DC-modulated T cells. CONCLUSION: KD treatment elicits immunosuppression against autoimmune liver injury by targeting VEGFR2, followed by diminishing the cross-talk of metabolism-related PI3K-AKT and inflammation-related JAK2-STAT3 pathways, and thereby disrupts DC-induced cross-priming of CD8+ T cell responses. (Hepatology 2016;64:2135-2150).


Assuntos
4-Butirolactona/análogos & derivados , Linfócitos T CD8-Positivos/efeitos dos fármacos , Comunicação Celular/efeitos dos fármacos , Células Dendríticas/efeitos dos fármacos , Hepatite Autoimune/tratamento farmacológico , Imunossupressores/uso terapêutico , Monossacarídeos/uso terapêutico , 4-Butirolactona/uso terapêutico , Animais , Linfócitos T CD8-Positivos/fisiologia , Comunicação Celular/fisiologia , Células Dendríticas/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL
11.
BMC Complement Altern Med ; 16: 80, 2016 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-26916550

RESUMO

BACKGROUND: Anoectochilus formosanus has been used as a Chinese folk medicine and is known as the "King of medicine" in Chinese society due to its versatile pharmacological effects such as anti-hypertension, anti-diabetes, anti-heart disease, anti-lung and liver diseases, anti-nephritis and anti-Rheumatoid arthritis. Kinsenoside is an essential and active compound of A. formosanus (Orchidaceae). However, the anti-arthritic activity of kinsenoside has still not been demonstrated. In the present study, we confirmed that the kinsenoside treatment rheumatoid arthritis induced by collagen-induced arthritis in mice. METHODS: Male DBA/1 J mice were immunized by intradermal injection of 100 µg of type II collagen in CFA. Kinsenoside was administered orally at a dose of 100 and 300 mg/kg once a day after 2nd booster injection. Paw swelling, arthritic score and histological change were measured. ELISA was used to measure cytokines including tumor necrosis factor alpha (TNF-α), interleukin-10 (IL-10), interleukin-17 (IL-17) and interferon-γ (IFN-γ) in the splenocyte according to the manufacturer's instructions. RESULTS: Compared with model group, kinsenoside significantly inhibited paw edema and decreased the arthritis score and disease incidence. Histopathological examination demonstrated that kinsenoside effectively protected bone and cartilage of knee joint from erosion, lesion and deformation versus those from the CIA group. Kinsenoside also decreased IL-1ß, TNF-α, and MMP-9 expression, and increased the expression of IL-10 in inflamed joints. The administration of kinsenoside significantly suppressed levels of TNF-α, IFN-γ, and IL-17, but increased concentrations of IL-10 in the supernatants of each of the splenocytes in CIA mice compared with that in the H2O-treated mice with CIA. Using flow cytometric analysis, we demonstrated that kinsenoside increases the population of CD4(+)CD25(+) regulatory T cells, thereby inhibiting the Th1 cell and B cell populations. Anticollagen IgG1 and IgG2a levels decreased in the serum of kinsenoside-treated mice. CONCLUSIONS: These results suggest that the administration of kinsenoside effectively suppressed inflammatory mediators' production and bone erosion in mice with collagen-induced arthritis showing the potential as an anti-arthritis agent.


Assuntos
4-Butirolactona/análogos & derivados , Anti-Inflamatórios/uso terapêutico , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide , Mediadores da Inflamação/metabolismo , Monossacarídeos/uso terapêutico , Orchidaceae/química , Linfócitos T/metabolismo , 4-Butirolactona/farmacologia , 4-Butirolactona/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Antirreumáticos/farmacologia , Antirreumáticos/uso terapêutico , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Colágeno Tipo II/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Edema , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/metabolismo , Articulação do Joelho/patologia , Masculino , Camundongos Endogâmicos DBA , Monossacarídeos/farmacologia , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
12.
J Ethnopharmacol ; 182: 221-34, 2016 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-26900126

RESUMO

ETHANOPHARMACOLOGICAL RELEVANCE: Opuntia dillenii Haw (Nagphana) traditionally used against inflammation. The present study addressed the anti-inflammatory activity of O. dillenii derived methanol extract, fractions and pure compounds and their underlying mechanism of action. MATERIALS AND METHODS: O. dillenii cladode methanol extract was subjected to vacuum liquid chromatography (VLC) furnishing two main fractions viz (T-1 and -2) leading to isolation of opuntiol (aglycone) and opuntioside (O-glucoside), respectively. Anti-inflammatory activity of extract, fractions, pure compounds and reference drugs were evaluated using: (1) arachidonic acid (AA) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced ear edema accompanied by histological studies of mice ear sections and phospholipase A2 (PLA2)-induced mice paw edema. (2) Carrageenan and glycogen-induced peritonitis in rodents. In parallel levels of leukotriene B4 (LTB4) and reactive oxygen species (ROS) were also determined via HPLC and fluoroemetrically using 2', 7'-dichlorodihydrofluorescein diacetate (DCFH-DA) dye, respectively. Additionally, levels of prostaglandin E2 (PGE2), tumor necrosis factor (TNF-α), interleukins IL-1ß and -6 were measured by ELISA assay. RESULTS: O. dillenii methanol extract, fractions and pure compounds reduced AA and TPA-induced ear punch weight in a dose dependent fashion. The corresponding IC50 values obtained also suppressed inflammatory features observed histologically. Furthermore, paw edema and peritonitis were also attenuated. Similar to indomethacin and diclofenac sodium, opuntioside reduced PGE2 levels of inflamed ear which was comparatively 1.3× better than opuntiol. However, opuntiol was more potent in reducing LTB4 levels in rat neutrophils with an IC50 value of 19±3.3µΜ, while opuntioside was ineffective. Opuntiol also effectively suppressed ROS (37%) and cytokine levels (TNF-α, IL-1ß and -6) by ~50% and comparable to dexamethasone. CONCLUSIONS: O. dillenii cladodes possess anti-inflammatory properties via inhibition of arachidonic acid metabolites and cytokines. Opuntiol (aglycone) emerged as a dual inhibitor of cyclooxygenase (COX) and lipooxygenase (LOX) pathways. It also suppressed ROS and cytokine levels. However, opuntioside manifested its selectivity towards COX (PGE2) pathway without affecting LTB4 levels. The present report describing the anti-inflammatory activity of opuntiol and opuntioside for the first time thereby, supporting and justifying the traditional use of O. dillenii against inflammation and may serve as lead compound in designing of new anti-inflammatory agents.


Assuntos
Anti-Inflamatórios/uso terapêutico , Ácidos Cumáricos/uso terapêutico , Edema/tratamento farmacológico , Monossacarídeos/uso terapêutico , Opuntia , Extratos Vegetais/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Ácido Araquidônico , Permeabilidade Capilar/efeitos dos fármacos , Carragenina , Ácidos Cumáricos/análise , Ácidos Cumáricos/farmacologia , Citocinas/metabolismo , Dinoprostona/metabolismo , Orelha/patologia , Edema/induzido quimicamente , Edema/metabolismo , Feminino , Pé/patologia , Leucotrieno B4/metabolismo , Masculino , Camundongos , Monossacarídeos/análise , Monossacarídeos/farmacologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Peritonite/induzido quimicamente , Peritonite/tratamento farmacológico , Fosfolipases A2 , Fitoterapia , Extratos Vegetais/análise , Extratos Vegetais/farmacologia , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Acetato de Tetradecanoilforbol
13.
Planta Med ; 82(5): 407-13, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26824620

RESUMO

The leaves of Echinodorus grandiflorus are traditionally used in Brazil to treat several inflammatory conditions, including arthritis. This study aimed to investigate the antiarthritis activity of the 70% ethanol extract of E. grandiflorus leaves and a standardized flavonoid-rich fraction in an antigen-induced arthritis model in mice. Previously immunized mice were treated per os with saline (control group), 70% ethanol extract (100-1000 mg/kg), or a flavonoid-rich fraction (0.7-7.2 mg/kg) 40 minutes before and 3 and 6 hours after the challenge with antigen into the knee joint. The administration of the 70% ethanol extract and flavonoid-rich fraction to mice significantly reduced neutrophil recruitment to the joint cavity and in periarticular tissue. The levels of chemokine (C-X-C motif) ligand 1, tumor necrosis factor-α, and interleukin-1ß quantified by the enzyme-linked immunosorbent assay (ELISA) in the periarticular tissue were also diminished in mice treated with the 70% ethanol extract and flavonoid-rich fraction, as well as mechanical hypernociception. Histological analysis confirmed that both the 70% ethanol extract and flavonoid-rich fraction suppressed joint inflammation and inhibited cartilage and bone destruction when compared to the control group. Our results demonstrate, for the first time, that E. grandiflorus has anti-inflammatory activity in an experimental arthritis model and highlights the role of flavonoids in the observed response.


Assuntos
Alismataceae/química , Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Experimental/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Animais , Brasil , Modelos Animais de Doenças , Flavonoides/uso terapêutico , Glicosídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Monossacarídeos/uso terapêutico , Folhas de Planta/química
14.
Nutr J ; 14: 116, 2015 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-26530312

RESUMO

BACKGROUND: Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) are poorly absorbed, short-chain carbohydrates that play an important role in inducing functional gut symptoms. A low-FODMAP diet improves abdominal symptoms in patients with inflammatory bowel disease and irritable bowel syndrome. However, there were no study for the effect of FODMAP content on gastrointestinal intolerance and nutritional status in patients receiving enteral nutrition (EN). METHODS: In this randomized, multicenter, double-blind, 14-day clinical trial, eligible hospitalized patients receiving EN (n = 100) were randomly assigned to three groups; 84 patients completed the trial (low-FODMAP EN, n = 30; moderate-FODMAP EN, n = 28; high-FODMAP EN, n = 26). Anthropometric and biochemical parameters were measured; stool assessment was performed using the King's Stool Chart and clinical definition. RESULTS: Baseline values were not significantly different among the three groups. After the 14-day intervention, diarrhea significantly improved in the low-FODMAP group than in the moderate- and high-FODMAP groups (P < 0.05). King's Stool scores in diarrhea subjects were significantly and steadily reduced in the low-FODMAP group compared with the other two groups (P for time and EN type interaction <0.05). BMI increased significantly in the low- and high-FODMAP groups during the intervention (P < 0.05 for both), and showed a trend toward increasing in the moderate-FODMAP group (P < 0.10). Serum prealbumin increased significantly in all groups by 14-day; by 3-day, it had increased to the levels at 14-day in the low-FODMAP group. At 14-day, serum transferrin had increased significantly in the moderate-FODMAP group. In addition, subjects were classified by final condition (unimproved, normal maintenance, diarrhea only improved, constipation only improved, and recurrent diarrhea/constipation improved). Seventy-five percent of the diarrhea improved group consumed the low-FODMAP EN formula. 38.5 and 46.2% of recurrent diarrhea/constipation improved group consumed the low- and moderate-FODMAP EN respectively. BMI significantly increased in all groups except the unimproved. Prealbumin levels significantly increased in the diarrhea-improved and recurrent diarrhea/constipation groups at 3-day and continued by 14-day, and in the constipation-improved group at 14-day. Transferrin levels significantly increased in the diarrhea-improved and recurrent diarrhea/constipation groups at 14-day. CONCLUSION: Low-FODMAP EN may improve diarrhea, leading to improved nutritional status and facilitating prompt recovery from illness.


Assuntos
Diarreia/dietoterapia , Nutrição Enteral/métodos , Fermentação , Pacientes Internados , Monossacarídeos/uso terapêutico , Estado Nutricional , Polissacarídeos/uso terapêutico , Dissacarídeos/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oligossacarídeos/uso terapêutico , Resultado do Tratamento
15.
Curr Top Med Chem ; 15(23): 2390-4, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26095241

RESUMO

The major role of liver glycogen is to supply glucose to the circulation maintaining the normal blood glucose level. In muscle and liver the accumulation and breakdown of glycogen are regulated by the reciprocal activities of glycogen phosphorylase and glycogen synthase. Glycogen phosphorylase catalyses the key step of glycogen degradation and its activity can be inhibited by glucose and its analogues. Obviously, any readily accessible inhibitor of glycogen phosphorylase can be used as a potential therapy of non-insulin-dependent or type 2 diabetes. Hepatic glycogen phosphorylase has been identified as a new target for drugs that control blood glucose concentration. In our experiments glucopyranosylidene-spirothiohydantoin (TH) was tested on the insulin sensitivity and blood glucose level of control and streptozotocin-treated rats. The streptozotocin-treated rats failed to gain weight and exhibited stable hyperglycemia (4.7 ± 0.5 mmol/L glucose in control vs. 7.8 ± 0.5 mmol/L) and low plasma insulin levels (9.6 ± 1.9 µIU/mL in control vs. 3.2 ± 2.2 µIU/mL). When insulin supplementation with slow-release implants (2 IU/day) was started 8 weeks after streptozotocin injection, blood glucose concentration remained suppressed, plasma insulin level dramatically increased and the insulin sensitivity restored. TH administration significantly reduced the high blood glucose concentration and restored the insulin sensitivity of STZtreated rats.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Glicogênio Fosforilase/antagonistas & inibidores , Hipoglicemiantes/uso terapêutico , Resistência à Insulina , Insulina/sangue , Monossacarídeos/uso terapêutico , Compostos de Espiro/uso terapêutico , Animais , Glicemia/análise , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/enzimologia , Glicogênio/metabolismo , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Insulina/uso terapêutico , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Monossacarídeos/administração & dosagem , Ratos Wistar , Compostos de Espiro/administração & dosagem , Estreptozocina
16.
Aliment Pharmacol Ther ; 41(12): 1256-70, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25903636

RESUMO

BACKGROUND: Dietary fibre supplements have been advocated for the management of chronic constipation (CC) and irritable bowel syndrome (IBS). Recently, a fermentable oligosaccharide, disaccharide, monosaccharide and polyol (FODMAP) restricted diet has been recommended for IBS. AIM: To systematically examine recent evidence for dietary interventions with fibre in CC and IBS and FODMAP-restricted diet in IBS, and provide recommendations. METHODS: We searched PUBMED, MEDLINE, OVID and COCHRANE databases from 2004 to 2014. Published studies in adults with CC and IBS and constipation-predominant IBS (IBS-C) that compared fibre with placebo/alternative and FODMAP-restricted diet with alternative were included. RESULTS: Of 550 potentially eligible clinical trials on fibre, 11 studies were found and of 23 potentially eligible studies on FODMAPs, six were found. A meta-analysis was not performed due to heterogeneity and methodological quality. Fibre was beneficial in 5/7 studies in CC and 3/3 studies in IBS-C. FODMAP-restricted diet improved overall IBS symptoms in 4/4 and IBS-C symptoms in 1/3 studies and three studies did not meet inclusion criteria. There were significant disparities in subject selection, interventions and outcome assessments in both fibre and FODMAPs studies. CONCLUSIONS: Fibre supplementation is beneficial in mild to moderate CC and IBS-C, although larger, more rigorous and long-term RCTs are needed (Fair evidence-Level II, Grade B). Although the FODMAP-restricted diet may be effective in short-term management of selected patients with IBS (Fair evidence-Level II, Grade C) and IBS-C (Poor evidence-Level III, Grade C), more rigorous trials are needed to establish long-term efficacy and safety, particularly on colonic health and microbiome.


Assuntos
Constipação Intestinal/terapia , Dietoterapia/métodos , Fibras na Dieta/administração & dosagem , Síndrome do Intestino Irritável/terapia , Adulto , Dissacarídeos/uso terapêutico , Gerenciamento Clínico , Fermentação , Humanos , Monossacarídeos/uso terapêutico , Oligossacarídeos/uso terapêutico , Polímeros/uso terapêutico
17.
Pharm Biol ; 53(11): 1632-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25856718

RESUMO

CONTEXT: Polygonum cuspidatum Sieb. Et Zucc. (Polygonaceae) has been traditionally used in folk medicine to treat various diseases. OBJECTIVE: This study investigates the ameliorative effects of physcion 8-O-ß-glucopyranoside (PSG) isolated from P. cuspidatum on learning and memory in dementia rats induced by Aß1-40. MATERIALS AND METHODS: Dementia rats were prepared by intracerebroventricular injection of Aß1-40. PSG (5, 10, 20, and 40 mg/kg/d, for 5 d) was administered orally. Ameliorative activity of PSG in dementia rats was evaluated by the Morris water maze (MWM) test, and its mechanisms were explored by evaluating AchE activity, levels of DA, NE, and 5-HT in hippocampus, and drebrin protein expressions in hippocampus. RESULTS: Our results indicated that PSG (5, 10, 20, and 40 mg/kg/d) significantly inhibited the prolonged latency in dementia rats (p < 0.05), and inhibitory rates were 16.5, 22.7, 33.0, and 44.8% after 5 d of learning, indicating that PSG improves learning and memory of dementia rats. Furthermore, PSG significantly decreased AchE activity (10, 20, and 40 mg/kg/d; p < 0.05), increased 5-HT (20 and 40 mg/kg/d, p < 0.05), NE (10, 20, and 40 mg/kg/d; p < 0.05), and DA levels (5, 10, 20, and 40 mg/kg; p < 0.05) in the hippocampus. Additionally, PSG obviously decreased the Aß contents in hippocampus (10, 20, and 40 mg/kg/d; p < 0.05), and up-regulated drebrin protein expressions (5, 10, 20, and 40 mg/kg/d; p < 0.05). CONCLUSIONS: PSG can significantly enhance learning and memory in Aß1-40-induced dementia rats, and the mechanisms may be related to increase levels of Ach, 5-HT, NE, and DA, decrease Aß contents, and up-regulation of drebrin proteins in hippocampus.


Assuntos
Peptídeos beta-Amiloides/toxicidade , Demência/tratamento farmacológico , Fallopia japonica , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Monossacarídeos/uso terapêutico , Fragmentos de Peptídeos/toxicidade , Animais , Demência/induzido quimicamente , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Emodina/análogos & derivados , Emodina/isolamento & purificação , Emodina/farmacologia , Emodina/uso terapêutico , Masculino , Aprendizagem em Labirinto/fisiologia , Memória/fisiologia , Monossacarídeos/isolamento & purificação , Monossacarídeos/farmacologia , Raízes de Plantas , Ratos , Ratos Sprague-Dawley , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologia , Resultado do Tratamento
18.
Nutrients ; 7(3): 1480-93, 2015 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-25734563

RESUMO

The antidiabetic effect of a hot water extract of stems of Salacia chinensis (SCE) was evaluated in vivo in KK-Ay mice, a typical type 2 diabetes mellitus mice model. Administration of CE-2 dietary feed containing 0.25 and/or 0.50% of SCE for three weeks to KK-Ay mice significantly suppressed the elevation of both blood glucose and HbA1c levels without significant changes in body weight or food intake. Glucose tolerance was improved by administration to KK-Ay mice for 27 days of AIN93M purified dietary feed containing 0.12% of SCE. No suppressive effect with respect to HbA1c level was observed when AIN93M/Glc dietary feed in which all digestible glucides were replaced with glucose was administered with SCE. Thus, α-glucosidase inhibitory activity approved as the mechanism of action of the antidiabetic effect of SCE by in vitro investigation was reconfirmed also in in vivo studies. Evaluation of the α-glucosidase inhibitory activity of the active constituents, salacinol (1), kotalanol (3), and neokotalanol (4), by employing human α-glucosidases revealed that these compounds inhibited them as potently (IC50 = 3.9-4.9 µM for maltase) as they inhibited rat small intestinal α-glucosidase. The principal sulfonium constituents (1-4) were highly stable in an artificial gastric juice. In addition, 1-4 were hardly absorbed from the intestine in an experiment using the in situ rat ligated intestinal loop model. The results indicate that these sulfoniums are promising leads for a new type of anti-diabetic agents.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores de Glicosídeo Hidrolases/uso terapêutico , Monossacarídeos/uso terapêutico , Fitoterapia , Extratos Vegetais/uso terapêutico , Salacia/química , Álcoois Açúcares/uso terapêutico , Sulfatos/uso terapêutico , Animais , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Modelos Animais de Doenças , Hemoglobina A Glicada/metabolismo , Inibidores de Glicosídeo Hidrolases/farmacologia , Humanos , Intestino Delgado/metabolismo , Masculino , Camundongos , Monossacarídeos/farmacologia , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley , Álcoois Açúcares/farmacologia , Sulfatos/farmacologia , Compostos de Sulfônio/farmacologia , Compostos de Sulfônio/uso terapêutico , alfa-Glucosidases/metabolismo
19.
Nutr Clin Pract ; 30(5): 665-82, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25694210

RESUMO

Irritable bowel syndrome (IBS) is a condition characterized by abdominal pain, bloating, flatus, and altered bowel habits. The role of dietary components in inducing IBS symptoms is difficult to explore. To date, foods are not considered a cause but rather symptom-triggering factors. Particular interest has been given to the so-called FODMAPs (fermentable oligo-, di-, and monosaccharides and polyols). We aimed to summarize the evidence from the most common approaches to manage suspected food intolerance in IBS, with a particular interest in the role of FODMAPs and the effects of a low FODMAP diet. We reviewed literature, consulting PubMed and Medline by using the search terms FODMAP(s), fructose, lactose, fructans, galactans, polyols (sorbitol, mannitol, maltitol, xylitol, erythritol, polydextrose, and isomalt), irritable bowel syndrome, and functional gastrointestinal symptoms. FODMAP-restricted diets have been used for a long time to manage patients with IBS. The innovation in the so-called FODMAP concept is that a global restriction should have a more consistent effect than a limited one in preventing abdominal distension. Even though all the potential low FODMAP diets provide good relief of symptoms in many patients, there is just a little relief in others. Several studies highlight the role of low FODMAP diets to improve symptoms in patients with IBS. The evidence on this dietary approach supports the hypothesis that a low FODMAP diet should be the first dietary approach. However, many points remain to be clarified, including the evaluation of possibly significant nutrition concerns.


Assuntos
Dieta , Carboidratos da Dieta/uso terapêutico , Síndrome do Intestino Irritável/dietoterapia , Monossacarídeos/uso terapêutico , Oligossacarídeos/uso terapêutico , Álcoois Açúcares/uso terapêutico , Fermentação , Humanos
20.
Med Chem ; 11(4): 317-28, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25557661

RESUMO

A brief history of the design of sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors is reviewed. The design of O-glucoside SGLT2 inhibitors by structural modification of phlorizin, a naturally occurring O-glucoside, in the early stage was a process mainly driven by biology with anticipation of improving SGLT2/SGLT1 selectivity and increasing metabolic stability. Discovery of dapagliflozin, a pioneering C-glucoside SGLT2 inhibitor developed by Bristol-Myers Squibb, represents an important milestone in this history. In the second stage, the design of C-glycoside SGLT2 inhibitors by modifications of the aglycone and glucose moiety of dapagliflozin, an original structural template for almost all C-glycoside SGLT2 inhibitors, was mainly driven by synthetic organic chemistry due to the challenge of designing dapagliflozin derivatives that are patentable, biologically active and synthetically accessible. Structure-activity relationships (SAR) of the SGLT2 inhibitors are also discussed.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Descoberta de Drogas/história , Hipoglicemiantes/síntese química , Hipoglicemiantes/história , Inibidores do Transportador 2 de Sódio-Glicose , Compostos Benzidrílicos/síntese química , Compostos Benzidrílicos/história , Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Desenho de Fármacos , Glucosídeos/síntese química , Glucosídeos/história , Glucosídeos/uso terapêutico , Glicosídeos , História do Século XX , História do Século XXI , Humanos , Hipoglicemiantes/uso terapêutico , Monossacarídeos/síntese química , Monossacarídeos/história , Monossacarídeos/uso terapêutico , Florizina/análogos & derivados , Florizina/síntese química , Florizina/história , Florizina/uso terapêutico , Transportador 2 de Glucose-Sódio/química , Transportador 2 de Glucose-Sódio/metabolismo , Relação Estrutura-Atividade
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